Clinical outcomes after 4.5 years of eliglustat therapy for <scp>Gaucher</scp> disease type 1: Phase 3 <scp>ENGAGE</scp> trial final results
Bibliographic record
Abstract
Abstract Eliglustat, an oral substrate reduction therapy, is approved for eligible adults with Gaucher disease type 1. In the Phase 3 ENGAGE trial of previously untreated adults with Gaucher disease type 1, eliglustat‐treated patients had statistically significant improvements in organ volumes and hematologic parameters compared with placebo in the 9‐month primary analysis. We report final outcomes by time on eliglustat among all patients who participated in the ENGAGE trial and extension. No patient deteriorated clinically or withdrew due to adverse events; 39/40 patients entered the open‐label extension period and 34/40 (85%) remained in the trial until completion or switching to commercial eliglustat after its approval (2.3–6 years). Clinically meaningful improvements in Gaucher disease manifestations were seen in all patients concomitant with reductions in pathological lipid substrate levels (glucosylceramide and glucosylsphingosine). Among patients with 4.5 years of eliglustat exposure, mean spleen volume decreased by 66% (from 17.1 to 5.8 multiples of normal [MN], n = 13), mean liver volume decreased by 23% (from 1.5 to 1.1 MN, n = 13), mean hemoglobin increased 1.4 g/dl (from 11.9 to 13.4 g/dl, n = 12), mean platelet count increased by 87% (from 67.6 to 122.6 × 109/L, n = 12), median chitotriosidase decreased by 82% (from 13 394 to 2312 nmol/h/ml, n = 11), median glucosylceramide decreased by 79% (from 11.5 to 2.4 μg/ml, n = 11), median glucosylsphingosine decreased by 84% (from 518.5 to 72.1 ng/ml, n = 10), and mean spine T‐score increased from −1.07 (osteopenia) to −0.53 (normal) (n = 9). The magnitude of improvement in Gaucher disease manifestations and biomarkers over time was similar among the full trial cohort. Eliglustat was well‐tolerated and led to clinically significant improvements in previously untreated patients with Gaucher disease type 1 during 4.5 years of treatment.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".